Maintenance therapy with aromatase inhibitors, such as anastrozole, delays or prevents disease progression in a subset of women with metastatic, hormone-receptor (HR)-positive breast cancer; however, the majority of women do not have long-term responses to these agents. Now, new data from a phase III trial (S0226) confirm the superior efficacy of the addition of the selective oestrogen receptor degrader fulvestrant to anastrozole versus anastrozole alone.
A total of 707 postmenopausal women who had not previously received chemotherapy, hormone therapy or immunotherapy for metastatic disease were randomized (1:1) to receive either anastrozole plus fulvestrant or anastrozole alone, with a primary end point of progression-free survival (PFS). After a median follow-up duration of 13.5 months (7 years in those without disease progression), median PFS was 13.5 months among women receiving anastrozole versus 15.0 months in those receiving anastrozole plus fulvestrant (HR 0.81, 95% CI 0.69–0.94; P = 0.007). Median overall survival (OS) was 49.8 months in patients receiving anastrozole plus fulvestrant versus 42.0 months among those in the anastrozole group (HR 0.82, 95% CI 0.69–0.98; P = 0.03). Data from subgroup analyses revealed no significant differences in OS among any of the subgroups, including those stratified by endocrine sensitivity, previous endocrine therapy, measurable disease or disease location.
Few new adverse events emerged in the extended follow-up period: patients in the anastrazole plus fulvestrant group had a slightly increased risk of grade ≥3 adverse events (15% versus 13%; P = 0.47), including musculoskeletal pain, fatigue and hot flushes. No new grade 4 or 5 adverse events were reported.
These data support the routine clinical use of anastrozole plus fulvestrant in women with HR-positive metastatic breast cancer. Notably, this trial provided a robust efficacy signal despite a substantial number of women (45%) crossing over to the anastrozole plus fulvestrant group, as permitted by the trial design.
Mehta, R. S. et al. Overall survival with fulvestrant plus anastrozole in metastatic breast cancer. N. Engl. J. Med. 380, 1226–1234 (2019)
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Sidaway, P. Fulvestrant enables better outcomes. Nat Rev Clin Oncol 16, 337 (2019). https://doi.org/10.1038/s41571-019-0211-7
Rethinking the combination treatment of fulvestrant and anastrozole for metastatic breast cancer: an integrated reanalysis of aromatase–estrogen receptor axis
Clinical and Translational Medicine (2019)